Alzheimer's disease (AD) represents the most common cause of dementia accounting for more than 50% of the cases. It is one of the three diseases which are the most expensive for society, together with cancer and cardiovascular diseases. Alzheimer's disease affects 35 million people worldwide (Querfurth et al. (2010) New England J. Med. 362:329-344). Its incidence doubles every 5 years after 65 years of age. Being closely associated with population ageing, AD is an important challenge for research teams.
Currently available medications can produce moderate symptomatic benefits, but at present no treatment is available that can cure AD or at least stop disease progression. Provided that, in the future, novel therapeutics with disease modifying properties become available, most benefit can be expected when the treatment will be started as early as possible in the course of the disease. Obviously, an essential prerequisite will be the availability of improved diagnostic tools allowing for reliable and early, optionally differential diagnosis. It appears that the pathological changes in the AD brain start many years before the first clinical symptoms become obvious (see e.g. Fagan et al. (2009) Ann. Neurol. 65:176-83).
Well documented AD biomarkers in cerebrospinal fluid that can support the clinical diagnosis are increased concentrations of total Tau and phosphorylated Tau protein as well as a selective decrease in Aβ1-42 peptide. Furthermore, brain imaging methods, such as Magnetic Resonance Tomography (MRT), Positron Emission Tomography (PET) and in vivo amyloid imaging can provide important additional information. Nevertheless, additional biomarkers or biomarker signatures and novel analytical methods are required to improve the early and/or differential diagnosis to reliably detect AD patients at early disease stages or at high risk.
Diagnostic tests are defined in terms of their sensitivity (defined by the percentage of patients suffering from the disease and tested as positive, in a population of patients identified as suffering from said disease using a reference test) and by their specificity (defined by the percentage of patients who do not suffer from the disease and who were tested as negative, in a population of patients identified as not suffering from said disease using a reference test). Diagnostic tests with a high sensitivity and a high specificity (close to 100%) are rare.
Accordingly, there is still a need for methods enabling a specific and sensitive diagnosis of Alzheimer's disease, in particular an early diagnosis of the disease, before the onset of clinical symptoms.